History Of Cervical Intraepithelial Neoplasia Research Articles

Cytology and HPV Co-Testing for Detection of Vaginal Intraepithelial Neoplasia: A Retrospective Study.

(1) Background: Vaginal intraepithelial neoplasia (VaIN) is a rare premalignant disease caused by persistent human papillomavirus (HPV) infection. Diagnosing VaIN is challenging; abnormal cytology and positive HPV tests are usually the first signs, but published data on their accuracy for detecting it are rare and contradictory. The aim of this study is to compare the results of hrHPV and cytology co-testing with the histological findings of the vagina. (2) Methods: In the certified Dysplasia Unit at Erlangen University Hospital, cytology and HPV samples from the uterine cervix or vaginal wall after hysterectomy were obtained between 2015 and 2023 and correlated with histological findings in biopsies from the vaginal wall. Women without vaginal biopsy findings or concomitant cervical disease were excluded. (3) Results: In all, 279 colposcopies in 209 women were included. The histological results were: benign (n = 86), VaIN I/vLSIL (n = 116), VaIN II/vHSIL (n = 41), VaIN III/vHSIL (n = 33), and carcinoma (n = 3). Accuracy for detecting VaIN was higher in women with previous hysterectomies. Positive HPV testing during colposcopy increased the likelihood for VaIN II/III/vHSIL threefold. The detection rate for VaIN III/vHSIL was 50% after hysterectomy and 36.4% without hysterectomy. (4) Conclusions: Women with risk factors for VaIN, including HPV-16 infection or prior HPV-related disease, need careful work-up of the entire vaginal wall. Hysterectomy for HPV-related disease and a history of cervical intraepithelial neoplasia (CIN) also increased the risk for VaIN II/III/vHSIL.

Enhancing long-term smoking abstinence among individuals with a history of cervical intraepithelial neoplasia or cervical cancer (Project ACCESS): protocol for a randomized clinical trial

BackgroundThe prevalence of smoking among cervical cancer survivors is high and evidence-based smoking cessation interventions are critically needed. This paper describes the study design, methods, and data analysis plans for a randomized clinical trial (RCT) designed to evaluate the efficacy of a novel, personally tailored SMS-delivered text-based digital treatment adjuvant designed to enhance the long-term efficacy of a “Motivation And Problem-Solving” (MAPS) approach for smoking cessation among individuals with a history of cervical intraepithelial neoplasia (CIN) or cervical cancer. MAPS is a phone counseling approach designed to facilitate long-term abstinence that comprises 6 counseling calls over 12 months. The current trial is evaluating the efficacy of MAPS+, which comprises all MAPS components plus a 24-month digital treatment adjuvant. This trial represents a logical extension of our previous RCT, which compared the efficacy of MAPS to a quitline control condition and found that MAPS resulted in greater than a 2-fold increase in smoking abstinence at 12 months (i.e., 26.4% vs. 11.9%). This treatment effect was no longer significant at 18 months, suggesting that efficacy dissipated as time from the end of treatment increased. The primary aim of the current trial is to compare the efficacy of MAPS + and ST in facilitating long-term abstinence.MethodsIndividuals who smoke and have a history of cervical cancer or CIN (N = 340) are recruited throughout Florida and randomly assigned to Standard Treatment [ST] or MAPS+. ST participants are electronically connected with the Florida Quitline. MAPS + consists of 6 proactive MAPS-based counseling calls over 12 months plus the novel, personally tailored, text message-based treatment adjuvant delivered over 24 months. All participants receive 12 weeks of combination nicotine replacement therapy (patch and lozenge) and are followed for 24 months. Participant recruitment commenced in December 2022 and is ongoing.DiscussionThis study builds on promising results from our recent trial which found that MAPS was associated with substantially higher abstinence from smoking at the end of the 12-month treatment period. Finding that this low-burden, personally tailored digital treatment adjuvant improves the long-term efficacy of MAPS would have important clinical and public health implications.Trial registrationClinical Trials Registry NCT05645146; https://clinicaltrials.gov/ct2/show/NCT05645146; Registered on December 9, 2022.

Efficacy of a Smoking Cessation Intervention for Survivors of Cervical Intraepithelial Neoplasia or Cervical Cancer: A Randomized Controlled Trial.

Women who smoke and have a history of cervical intraepithelial neoplasia (CIN) or cervical cancer represent a vulnerable subgroup at elevated risk for recurrence, poorer cancer treatment outcomes, and decreased quality of life. The purpose of this study was to evaluate the long-term efficacy of Motivation And Problem Solving (MAPS), a novel treatment well-suited to meeting the smoking cessation needs of this population. Women who were with a history of CIN or cervical cancer, age 18 years and older, spoke English or Spanish, and reported current smoking (≥100 lifetime cigarettes plus any smoking in the past 30 days) were eligible. Participants (N = 202) were recruited in clinic in Oklahoma City and online nationally and randomly assigned to (1) standard treatment (ST) or (2) MAPS. ST consisted of repeated referrals to a tobacco cessation quitline, self-help materials, and combination nicotine replacement therapy (patch plus lozenge). MAPS comprised all ST components plus up to six proactive telephone counseling sessions over 12 months. Logistic regression and generalized estimating equations evaluated the intervention. The primary outcome was self-reported 7-day point prevalence abstinence from tobacco at 18 months, with abstinence at 3, 6, and 12 months and biochemically confirmed abstinence as secondary outcomes. There was no significant effect for MAPS over ST at 18 months (14.2% v 12.9%, P = .79). However, there was a significant condition × assessment interaction (P = .015). Follow-up analyses found that MAPS (v ST) abstinence rates were significantly greater at 12 months (26.4% v 11.9%, P = .017; estimated OR, 2.60; 95% CI, 1.19 to 5.89). MAPS led to a greater than two-fold increase in smoking abstinence among survivors of CIN and cervical cancer at 12 months. At 18 months, abstinence in MAPS declined to match the control condition and the treatment effect was no longer significant.

Intake of food groups and cervical cancer in women at risk for cervical cancer: A nested case-control study.

Background:The risk of cervical cancer was reported to be influenced by dietary components. This study aimed to illustrate the association between cervical cancer with the intake of food groups in women with a history of cervical neoplasia.Methods:This nested case-control study was conducted in 558 people with a history of cervical intraepithelial neoplasia (CIN), including 279 women with cervical cancers and 279 controls with low-grade squamous intraepithelial lesions (LSIL). A validated food frequency questionnaire (FFQ) was used to assess the intake of food groups.Results:The intake of fruits and vegetables in the case group was significantly lower than the control group (P=0.001). Low intake of dairy products, vegetables, and fruits was associated with cervical cancer risk (OR=4.67; 95% CI 1.2-9.49, P=0.001; OR=9.75, 95% CI 1.36-19. 51, P=0.001; and OR=4.82, 95% CI 1.09-7.25, P=0.001, respectively). After adjusting for age, family history, age at first menstruation, number of children, history of vaginal infection, and age at first sexual intercourse, the results were still significant. Additional adjustments to BMI did not change the results.Conclusion:The results indicate that the risk of cervical cancer can be affected by the intake of certain food groups. Further longitudinal studies are needed to confirm these findings and determine the underlying mechanism of the influence of dietary components on cervical cancer risk.

Association Between Human Papillomavirus Infection Among Pregnant Women and Preterm Birth

Preterm birth remains a leading cause of perinatal mortality and lifelong morbidity worldwide. The cause of most preterm births is unknown, although several infectious processes have been implicated. To assess whether human papillomavirus (HPV) infection, a frequent infection among women of childbearing age, is associated with preterm birth. The prospective HERITAGE cohort study was conducted at 3 academic hospitals in Montreal, Québec, Canada, among 899 pregnant women recruited between November 8, 2010, and October 16, 2016. Follow-up was completed on June 15, 2017. Statistical analysis was conducted from February 6, 2020, to January 21, 2021. Vaginal HPV DNA detection in the first and third trimesters of pregnancy and placental HPV infection. The main outcome was preterm birth (defined as a live birth or stillbirth between 20 weeks and 0 days and 36 weeks and 6 days of gestation). The association between HPV DNA detection and preterm birth was measured using logistic regression. Odds ratios (ORs) and 95% CIs were adjusted by inverse probability of treatment weights of the propensity score. The study included 899 women (mean [SD] age, 31.3 [4.6] years [range, 19-47 years]) with singleton pregnancies. A total of 378 women (42.0%) had HPV DNA detected in vaginal samples collected during the first trimester, and it was detected in 91 of 819 placentas (11.1%) at delivery. Fifty-five participants experienced preterm birth (38 spontaneous and 17 medically indicated). Persistent vaginal HPV-16/18 detection was significantly associated with all preterm births (adjusted OR [aOR], 3.72; 95% CI, 1.47-9.39) and spontaneous preterm births (aOR, 3.32; 95% CI, 1.13-9.80), as was placental HPV infection (all preterm births: aOR, 2.53; 95% CI, 1.06-6.03; spontaneous preterm births: aOR, 2.92; 95% CI, 1.09-7.81). Results were similar when restricting the analysis to participants without a history of cervical intraepithelial neoplasia treatment. The study's results suggest that persistent HPV-16/18 infection is associated with an increased risk of preterm birth, independent of cervical treatment. Future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth.

Management of abnormal results of the cervical screening during pregnancy

Nowadays, it has been registered an increased trend of detection for gynecological malignancies during pregnancy, mostly due to increased maternal age, cervical cancer being the most frequent malignancy in pregnancy. About 3% of the cervical cancer cases are diagnosed during pregnancy. The clinical manifestations depend of the stage and the lesion size, ranging from complete asymptomatic to vaginal bleeding or discharge, pelvic pain and chronic anemia. The screening of cervical cancer during pregnancy does not differ from the one of the nonpregnant patient, and should include cervical cytology and HPV testing, according to the national health policy. For selected cases, colposcopy and cervical biopsy can be performed in order to exclude the invasion. Given the physiological changes that occur to the cervix during the gestational period, the examination of the Pap smears and the colposcopies should be done by experienced physicians. Endometrial biopsy, endocervical curettage and the excisional treatment without biopsy are forbidden during pregnancy. The indications of cervical conization are limited for high-grade squamous intraepithelial lesions (HSIL) with unsatisfactory colposcopy and for those with suspicion or evidence of invasive disease. Otherwise, the procedure should be postponed until the postpartum period. Regarding the natural history of cervical intraepithelial neoplasia (CIN) during pregnancy, it has been shown that most of the lesions remain stable during pregnancy, but only a small rate (less than 5% of cases) have a more aggressive evolution, therefore it is important to have an adequate follow-up and management.

First-in-Human Phase I Clinical Trial of an SFV-Based RNA Replicon Cancer Vaccine against HPV-Induced Cancers

A first-in-human phase I trial of Vvax001, an alphavirus-based therapeutic cancer vaccine against human papillomavirus (HPV)-induced cancers was performed assessing immunological activity, safety, and tolerability. Vvax001 consists of replication-incompetent Semliki Forest virus replicon particles encoding HPV16-derived antigens E6 and E7. Twelve participants with a history of cervical intraepithelial neoplasia were included. Four cohorts of three participants were treated per dose level, ranging from 5 × 105 to 2.5 × 108 infectious particles per immunization. The participants received three immunizations with a 3-week interval. For immune monitoring, blood was drawn before immunization and 1 week after the second and third immunization. Immunization with Vvax001 was safe and well tolerated, with only mild injection site reactions, and resulted in both CD4+ and CD8+ T cell responses against E6 and E7 antigens. Even the lowest dose of 5 × 105 infectious particles elicited E6/E7-specific interferon (IFN)-γ responses in all three participants in this cohort. Overall, immunization resulted in positive vaccine-induced immune responses in 12 of 12 participants in one or more assays performed. In conclusion, Vvax001 was safe and induced immune responses in all participants. These data strongly support further clinical evaluation of Vvax001 as a therapeutic vaccine in patients with HPV-related malignancies.

Cytology-based screening for anal intraepithelial neoplasia in women with a history of cervical intraepithelial neoplasia or cancer.

High-risk human papillomavirus (HPV) has been identified in the pathogenesis of anal cancer. The purpose of this study was to assess the prevalence of abnormal anal cytology and HPV in women aged ≥40 years who have a history of high-grade cervical squamous intraepithelial lesion (SIL) or cancer and to estimate the prevalence of anal intraepithelial neoplasia (AIN) using cytology as the primary screening modality. Women who had a history of high-grade cervical SIL or cancer and were ≥40 years of age were included in this prospective study. Anal cytology with HPV-DNA testing was performed. All patients with abnormal anal cytology were referred for high-resolution anoscopy (HRA), and abnormal lesions were biopsied and treated if pathologically confirmed. Abnormal anal cytology correlated with HPV status, HRA findings, and clinical and demographic characteristics. A total of 317 women completed the study. Of these, 96 (30.3%) had abnormal anal cytology (high-grade SIL, 12.5%; low-grade SIL, 19.8%; atypical squamous cells, cannot exclude high-grade SIL, 6.3%; atypical squamous cells of undetermined significance, 61.5%) and 101 (31.9%) were HPV-DNA-positive. There was a significant association between abnormal cytology results and the presence of high-risk HPV. Of the 96 patients with abnormal cytology, 30 (31.3%) had biopsy-proven AIN on HRA, representing 9.5% of the total patient cohort; of these, 10 (33.3%) had low-grade AIN and 20 (66.7%) had high-grade AIN. Older age and smoking were significant risk factors for abnormal anal cytology. Women aged ≥40 years with a history of high-grade cervical SIL or cancer have a high rate of AIN. Screening for anal cancer may therefore be considered in this patient population. The optimal screening approach should be addressed in future studies.

The risk of cervical cancer after cervical intraepithelial neoplasia grade 3: A population-based cohort study with 80,442 women

ObjectiveTo estimate the risk of cervical cancer in women with a history of cervical intraepithelial neoplasia (CIN) grade 3 and to review the compliance with post-treatment follow-up. MethodsA population-based retrospective cohort study including 80,442 women with a median follow-up of 15.8 years, and 1,278,297 person years. Women with CIN3 between 1990 and 2010 were identified from the Dutch Pathology Registry (PALGA) and linked to the general female population from the Netherlands Cancer Registry. Cases of recurrent CIN3 and cervical cancer, defined as occurrence minimally two years post-treatment, were identified until 2016. Standardized incidence ratios (SIRs) were calculated for the risk of cervical cancer. Results1554 women (1.9%) developed recurrent CIN3 and 397 women (0.5%) cervical cancer. Women with CIN3 were associated with a twofold increased risk of cervical cancer (SIR 2.29; 95%CI 2.07–2.52) compared with the general female population. Women aged ≥50 years during CIN3 diagnosis had a sevenfold and women with recurrent CIN3 a ninefold increased risk of developing cervical cancer. The increased risk up to 20 years of follow-up seems to be mostly attributable to ageing. 37.0% of women who developed cervical cancer after CIN3 did not complete the advised post-treatment follow-up. ConclusionsWomen with CIN3 have a long-lasting twofold increased risk of developing cervical cancer, even when they complete the post-treatment follow-up and adhere to the regular screening program. This risk increases with CIN3 diagnosis at older age, further ageing during follow-up and in women with recurrent CIN3. Studies on optimizing follow-up strategies are warranted.

Risk Factors for Anal Dysplasia among Privately Insured HIV-Negative Women

Objective: To examine the relationship between anogenital abnormalities and the development of anal dysplasia among Human Immunodeficiency Virus (HIV)-negative women. Methods: This retrospective matched case-control study used administrative data from the 2009-2014 Clinformatics Data Mart. Cases were selected according to the International Classification of Diseases, Ninth Revision, using Clinical Modification codes for carcinoma in situ of the anal canal or anus unspecified, anal intraepithelial neoplasia 1 and 2, abnormal glandular Papanicolaou (Pap) smear of the anus, or Pap smears of the anus with atypical squamous cells, squamous intraepithelial lesions, or cytological evidence of malignancy. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals for the risk of anal dysplasia. Results: The study included 3,384 HIV-negative women (846 cases and 2,538 controls), mean age 50.1 ± 11.9 years. The odds of being a smoker, having cervical intraepithelial neoplasia (CIN), or anogenital warts were higher for HIV-negative women with anal dysplasia than for those without anal dysplasia (OR =2.5-16.3). Conclusions: HIV-negative women with anal dysplasia are more likely to have concomitant human papillomavirus (HPV)-related CIN and anogenital warts than women without anal dysplasia. The presence of HPV-associated lesions might have implications for future screening recommendations. HIV-negative women with a history of CIN and anogenital warts could benefit from anal dysplasia/anal cancer screening. Gaining a better understanding of the natural history of anal HPV infections will provide tools to better treat and counsel patients with anal dysplasia.

Anal human papillomavirus infection in HIV-positive men and women at two opportunistic infections clinics in Harare, Zimbabwe

BackgroundHIV-infected individuals are at increased risk of anal cancer; in the majority of cases this is linked to human papillomavirus (HPV) infection. Anal cancer screening is not routinely offered in Zimbabwe.MethodsA cross-sectional study was performed on 152 patients (88 females; 64 males) attending Opportunistic Infection Clinics at 2 tertiary hospitals between November 2014 and June 2015. Demographic data, immunological parameters and behavioural characteristics were collected. An anal swab was collected from each patient for HPV genotype testing. HPV testing was performed using MY09/MY11 PCR, followed by typing using the dot blot method.ResultsThe mean age was 39.6 years (range, 18–69 years). Median CD4 count was 375 cells/μL. 96% were on antiretroviral therapy. Only one patient identified as a man who has sex with men. Of 122 samples tested for HPV, 54 were positive (44%). HPV was three times more common in females (60%) than males (20%). Being HPV-positive was associated with history of perianal warts, history of cervical intraepithelial neoplasia and having more than ten lifetime sexual partners. The most commonly detected high-risk HPV genotypes were HPV-58 (13%), HPV-31 (11%) and HPV-16 (9%). Nine patients harboured multiple high-risk HPV types. The two most commonly detected low-risk genotypes were HPV-11 (17%) and HPV-53 (11%).ConclusionOverall anal HPV prevalence was 44% in this mostly heterosexual HIV-positive population. Oncogenic HPV types accounted for almost half of infections, supporting the need for surveillance of anal cancer in this population.

High-risk HPV detection and associated cervical lesions in a population of French menopausal women

BackgroundWith population ageing, post-menopausal women represent a new group to be considered in cervical cancer screening strategies, including the significance of High Risk (HR)-HPV detection. ObjectivesA retrospective analysis was conducted in a cohort of 406 menopausal women attending routine gynaecological consultation at the Hospital of Montpellier (France). Study designAll women benefited from a cervical smear and HR-HPV detection using Hybrid Capture 2 (HC2) test. The prevalence of cytological abnormalities, HR-HPV detection and risk factors associated with HR-HPV detection were analyzed. Evolution of both tests was evaluated in a sub-group of women with adequate follow-up. ResultsFive women (1.2%) had an abnormal cervical smear at baseline. HR-HPV was detected in 40 women (9.9%), including 36 women with normal cytology (9%). Risk factors associated with HR-HPV detection at enrolment were a previous history of Cervical Intraepithelial Neoplasia and a high socio-economic level, but not hormone replacement therapy. When cytology and HR-HPV detection were negative at enrolment, both remained negative for 95% (230/241) of women during follow-up (median duration of follow-up: 60 months). HR-HPV persistence was observed for 55% (18/33) of women with normal cytology and positive HR-HPV test. Finally, all women with a final diagnosis of high-grade (CIN2+) cervical lesion (N = 7) had a positive HR-HPV test with or without abnormal cytology. ConclusionsHR-HPV was detected in 9.9% of menopausal women. HR-HPV detection was a better predictor of CIN2+ lesions than cytology in this population. Women with previous CIN history should benefit from HR-HPV testing and need long term follow-up.

Comparison of cervical cancer screening among women with and without hysterectomies: a nationwide population-based study in Korea

BackgroundCervical cancer screening is not recommended for women who underwent hysterectomy with no history of cervical intraepithelial neoplasia (CIN) of grade 2 or higher. We aimed to determine the cervical cancer screening rate in Korean women who underwent hysterectomies and compare it to that in women with intact uteri.MethodsWe used data from the 2014–2016 Korean National Cancer Screening Survey; 6807 women aged 30–74 years were included in the study. Participants were asked about their experiences with cervical cancer screening, hysterectomy status, and other variables associated with cancer screening.ResultsThe screening rates among women who have undergone a hysterectomy vs. those who have not during the past 2 years were 61.8% (95% confidence interval [CI], 58.8–64.9) and 64.7% (95% CI, 64.1–65.3), respectively. Among younger women (30–44 years) and women with a family history of cancer, those with hysterectomies showed a higher cervical cancer screening rate than those without (77.8% vs. 57.1% and 75.0% vs. 67.1%, respectively).ConclusionsDespite available evidence and clinical recommendations, a considerable number of Korean women who no longer have a cervix continue to undergo unnecessary cervical cancer screening. It is necessary to identify the exact underlying causes for this phenomenon, and systematic efforts are required to prevent unnecessary screening for women who have undergone a hysterectomy.

Influence of age on histologic outcome of cervical intraepithelial neoplasia during observational management: results from large cohort, systematic review, meta-analysis

Aim of this study was to investigate the histologic outcome of cervical intraepithelial neoplasia (CIN) during observational management. Consecutive women with histologically verified CIN and observational management were included. Histologic findings of initial and follow-up visits were collected and persistence, progression and regression rates at end of observational period were assessed. Uni- and multivariate analyses were performed. A systematic review of the literature and meta-analysis was performed. In 783 women CIN I, II, and III was diagnosed by colposcopically guided biopsy in 42.5%, 26.6% and 30.9%, respectively. Younger patients had higher rates of regression (p < 0.001) and complete remission (< 0.001) and lower rates of progression (p = 0.003). Among women aged < 25, 25 < 30, 30 < 35, 35 < 40 years, and > 40 years, regression rates were 44.7%, 33.7%, 30.9%, 27.3%, and 24.9%, respectively. Pooled analysis of published data showed similar results. Multivariable analysis showed that with each five years of age, the odds for regression reduced by 21% (p < 0.001) independently of CIN grade (p < 0.001), and presence of HPV high-risk infection (p < 0.001). Patient’s age has a considerable influence on the natural history of CIN – independent of CIN grade and HPV high-risk infection. Observational management should be considered for selected young patients with CIN.

Pregnancy outcome after cervical conisation: A 2nd retrospective cohort study in the Leuven University Hospital

ObjectiveTo evaluate whether the dimensions of the cones removed during large loop excision of the transformation zone have decreased over time. Secondly, whether these changes were associated with a lower risk of obstetrical harms on a subsequent pregnancy. Study designA retrospective matched cohort study was performed in a tertiary referral unit in Belgium. A total of 97 women were identified from a database of women who underwent excisional treatment for cervical precancer between January 1st, 2004 and December 31st, 2012, and delivered before December 31st, 2014. The control group consisted of 120 non-treated women who had no history of cervical intra-epithelial neoplasia. Data on smoking status; gestational age at delivery; number of conisations; time interval between treatment and pregnancy; dimensions of the cone; severity of the lesion; and the extra resection of endocervical tissue were collected. These data were compared with those from a previous similar study at the University Hospital of Leuven in 2009, which database we enriched with information on the cone dimensions. Main outcome variables were gestational age at delivery, birthweight and neonatal condition at birth. ResultsOnly a significant lower birthweight could be found in the treated group compared to the control group (3364g [95% CI 3094–3290] versus 3364g [95% CI 3253–3475], P=0.023). The current study showed no increase in preterm birth rate after conisation and no relationship between volume or depth of the cone and preterm birth could be found. Over the period 1999–2014, a significant decrease in all dimensions was observed: on average −0.3mm, −0.3mm, −0.4mm and −132mm3 per year, for the depth, anteroposterior and transverse diameter and the volume, respectively. ConclusionsOur two successive studies showed a significant trend towards smaller cones which was accompanied by a decrease in preterm birth after excisional treatment. The clinician could limit the size of the cone to avoid obstetrical harms, but needs to be aware of the oncological safety as well.

Histological Follow-Up in Patients with Atypical Glandular Cells on Pap Smears.

Context:Atypical glandular cells (AGCs) result in the Papanicolaou (Pap) smear may be associated with significant genital and nongenital neoplastic processes.Aims:To evaluate the underlying histopathology in women who had AGCs on Pap smears.Settings and Design:Retrospective cross-sectional study.Patients and Methods:Clinicopathological data of patients who had AGC on Pap smears and underwent histological workup between January 2004 and December 2014 were retrieved from the computerized database of a tertiary care center. Patients with a prior history of cervical intraepithelial neoplasia or gynecological cancer were excluded.Statistical Analysis Used:Chi-square test or Fisher's exact tests were used as appropriate.Results:Cytological examination of the uterine cervix was carried out in 117,560 patients. We identified 107 patients (0.09%) with AGC and 80 of those with histological follow-up were included in the study. The median age at diagnosis was 47 years (range, 18–79), and 32 women (40%) were postmenopausal, while 56 (70%) had gynecological symptoms. Significant preinvasive or invasive lesions on pathological examination were detected in 27 (33.8%) patients, including 12 endometrial adenocarcinomas (15%), 8 cervical carcinomas (10%), 3 cervical intraepithelial neoplasia II/III (3.75%), 2 ovarian adenocarcinomas (2.5%), and 2 metastatic tumors (2.5%). Univariate analysis showed that postmenopausal status (P < 0.001), age >50 years old (P < 0.001), having symptoms at the time of admission (P = 0.041), and AGC “favor neoplasia” smear results (P = 0.041) were the clinical factors associated with significant pathological outcome.Conclusions:Patients with AGC on Pap smears should be evaluated vigilantly with histological workup, especially if they are postmenopausal or symptomatic.

Influence of Human Papillomavirus Infection on the Natural History of Cervical Intraepithelial Neoplasia 1: A Meta-Analysis.

Objective To provide a scientific basis for the prevention and treatment of cervical intraepithelial neoplasia grade 1 (CIN1). This study evaluated the impact of human papillomavirus (HPV) infection on the natural history of CIN1. Methods Electronic databases of Cochrane Library, EMBASE, PubMed, CNKI, CBM, and Wanfang were searched in April 2016. The eligibility criteria were documented by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We used the Newcastle-Ottawa scale (NOS) to assess study quality. Results Thirty-eight studies out of 3,246 identified papers were eligible for inclusion. The risk of CIN1 progression (relative risk [RR]: 3.04; 95% confidence interval [CI]: 2.41–3.83; P < 0.00001) and persistence (RR: 1.48; 95% CI: 1.17–1.87; P = 0.001) was higher in the HPV-positive group than HPV-negative group. Specifically, the risk of CIN1 progression (RR: 13.91; 95% CI: 3.46–55.90; P = 0.000) was higher among persistent high-risk HPV-positive patients and the ratio of CIN1 regression (RR: 0.65; 95% CI: 0.59–0.71; P < 0.00001) was lower in the HPV-positive group than HPV-negative group. Conclusion HPV infection resulted in an increased risk of CIN1 progression and decreased disease reversibility. Persistent high-risk HPV infection resulted in a further increased risk of CIN1 progression.

Feasibility of Quadrivalent HPV Vaccination as Immunologic Booster to Prevent Relapses In an Italian Cohort of Women Treated for Cervical Intraepithelial Neoplasia (CIN)

It is clear in Literature the effectiveness of HPV (Human Papilloma Virus) vaccine in women when administered before first sexual intercourse whit reduced benefit in those who are already HPV positive. What remains to be clarified is whether the HPV vaccines have any impact on HPV infections and any benefit in women who have been previously treated for pre-invasive cervical disease. HPV vaccine is currently indicated as preventive tool for cervical cancer, cervical and vulvar dysplasia and also genital warts. So it is possible to assume that it could play a preventive role against clinical relapses of these diseases. The aim of our study is evaluate the feasibility of HPV quadrivalent vaccine in an Italian cohort of women under 45 years of age whit previous history of CIN and evaluate the effectiveness of HPV vaccine as a tool also to prevent recurrent disease.

Cumulative High-Grade Squamous Intraepithelial Lesion Rate and Need for Surgical Intervention of Atypical Squamous Cells of Undetermined Significance Cytology-Diagnosed Patients: A Prospective Study

Objective: Τhe study aimed to study the rate of atypical squamous cells of undetermined significance (ASCUS) that progressed to high-grade squamous intraepithelial lesions (HGSIL), as well as the number of patients who finally necessitated a surgical intervention during follow-up. Methods: A prospective study was conducted on patients admitted for colposcopy during 2007-2012. We exclusively included those who presented with newly ASCUS diagnosis, while patients with a history of cervical intraepithelial neoplasia (CIN) were excluded. Primary end points were the cumulative rate of HGSIL during follow-up and the rate of surgical procedures performed because of such lesions. Results: There were 134 ASCUS cases included. Overall, there were 48 (35.8%) surgical excision procedures performed to treat or eliminate HGSIL during the follow-up period. According to the final histopathology of surgical specimens, the cumulative rate of CIN2 or higher cervical lesions was 28.4% (n = 38). Conclusion: The cumulative rate of CIN2+ during follow-up period was almost 30% for patients with ASCUS, with the necessity for interventional treatment being even higher.

Natural history of cervical intraepithelial neoplasia in pregnancy: postpartum histo-pathologic outcome and review of the literature.

BackgroundTo study the natural history of cervical intraepithelial neoplasia (CIN) during pregnancy and to compare the rates of persistence, progression and regression of CIN by colposcopically guided biopsy (CGB) during pregnancy with outcome in non-pregnant-women.MethodsA retrospective analysis of all pregnant women diagnosed with CIN at our outpatient clinic between 2005 and 2010 was performed. A CGB for histo-pathological analysis was obtained in all participants and observational management was performed. The histo-pathologic findings of initial and postpartum visits were collected. Rates of persistence, progression and regression of CIN were assessed. Results were compared to a matched control group of non-pregnant women where observational management was performed for at least three months. In addition a review of the literature and pooled analysis of published data was performed.ResultsA total of 51 pregnant women with CIN were included into analysis. CIN 1, 2, and 3 was diagnosed by CGB in 33.3, 13.7 and 52.9 % of all pregnant women, respectively. The postpartum histo-pathologic evaluation of the pregnant cohort revealed a significantly higher tendency to spontaneous regression (56.9 versus 31.4 %, p = 0.010) and a considerably, but not significantly higher complete remission rate (41.2 versus 27.5 %, p = 0.144) when compared to the non-pregnant cohort. In addition, we observed a significantly lower CIN persistence rate than in the non-pregnant cohort (39.2 versus 58.8 %, p = 0.048). The progression rate was notably low in the pregnant cohort (3.9 %) and no progression to invasive cancer was observed.ConclusionsCIN lesions show considerably high spontaneous regression rates postpartum. Once presence of invasive cancer is ruled out definitive treatment can be deferred to the postpartum period.